The work detailed in this proposal is designed to elucidate the mechanisms by which opioid receptors regulate ion channels and synaptic communication.An associated aim is to understand the regulation of neuronal Ca signals in general and the role of Ca in determining the viability of neurons under normal and pathological conditions. The major areas of research will be: 1) What are the structures and properties of neuronal voltage sensitive Ca channels? How can these channels be regulated by opioid and other receptors? How do G-proteins participate in this process? How does this process contribute to the phenomenon of presynaptic inhibition? 2) How do opioid and other receptors regulate neuronal K channels? How are G-proteins involved in this process? How do these details differ from the regulation of Ca channels? 3)How are neuronal Ca signals regulated by opioid and other receptors? How do Ca and other intracellular mediators such as free radicals contribute to the death of neurons in different circumstances ? What are the relative roles of necrosis and apoptosis in these processes? These studies will involve the use of biophysical,biochemical and molecular biological techniques. It is hoped that this research will provide us with further information on the way that opioid drugs can regulate the activity of nerve cells.